Abstract
Oxidative stress and subsequent nucleus pulposus (NP) cell apoptosis are important contributors to the development of intervertebral disc degeneration (IDD). Emerging evidences show that long noncoding RNAs (lncRNAs) play a role in the pathogenesis of IDD. In this study, we investigated the role of lncRNA ANPODRT (anti-NP cell oxidative damage-related transcript) in oxidative stress and apoptosis in human NP cells. We found that ANPODRT was downregulated in degenerative NP tissues and in NP cells treated with tert-butyl hydroperoxide (TBHP, the oxidative stress inducer). ANPODRT overexpression alleviated oxidative stress and apoptosis in NP cells exposed to TBHP, while ANPODRT knockdown exerted opposing effects. Mechanistically, ANPODRT facilitated nuclear factor E2-related factor 2 (Nrf2) accumulation and nuclear translocation and activated its target genes by disrupting the kelch-like ECH-associated protein 1- (Keap1-) Nrf2 association in NP cells. Nrf2 knockdown abolished the antioxidative stress and antiapoptotic effects of ANPODRT in NP cells treated with TBHP. Collectively, our findings suggest that ANPODRT protects NP cells from oxidative stress and apoptosis, at least partially, by activating Nrf2 signaling, implying that ANPODRT may be a potential therapeutic target for IDD.
Highlights
Low back pain (LBP), one of the most common health issues, is a leading cause of disability worldwide and results in an enormous global economic and public health burden [1]
We showed that anti-NP cell oxidative damage-related transcript (ANPODRT) alleviates oxidative stress and apoptosis in human nucleus pulposus (NP) cells, and the activation of the kelch-like ECH-associated protein 1- (Keap1-)nuclear factor E2-related factor 2 (Nrf2) signaling cascade is involved in this process
TBHP treatment downregulated ANPODRT in a dose- and time-dependent manner in human NP cells (Figures 1(c) and 1(d)). These results indicate that ANPODRT is potentially associated with intervertebral disc degeneration (IDD)
Summary
Low back pain (LBP), one of the most common health issues, is a leading cause of disability worldwide and results in an enormous global economic and public health burden [1]. Intervertebral disc (IVD) degeneration (IDD) and secondary pathomorphological changes in spine structure are widely acknowledged as the major causes of LBP [2, 3]. Excessive NP cell apoptosis disrupts normal metabolic activity within the NP, disrupting the normal IVD structure and physiological function, which is a key contributor to IDD initiation and progression [5, 6]. Oxidative stress and its induced mitochondrial pathway play an important role in NP cell apoptosis and IDD [10,11,12,13]. We and others have previously reported that amelioration of oxidative stress and subsequent NP cell apoptosis has a therapeutic effect on IDD progression [14,15,16]. An understanding of the underlying pathway regulating oxidative stress and subsequent NP cell apoptosis would significantly benefit IDD treatment
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